最新刊期
卷 49 ， 期 6 ， 2024
- “在劳力型热射病院前处置领域，专家归纳出十大误区并提出正确方案，旨在降低EHS的发生率、致残率及致死率。”
摘要：Exertional heat stroke (EHS) is the most serious and life-threatening acute heat-related illness. It can develop from heat-related illnesses, and the prehospital management is a crucial in the diagnosis and treatment of EHS. The prognosis of EHS patients is largely determined by the rapid recognition, effective cooling, and standardized transportation during the prehospital period. Extensive research has demonstrated that medical security personnel still have fatal misconceptions in the prehospital recognition and management of EHS, mainly due to the lack of recognition and inappropriate treatment. This review summarizes the top 10 misconceptions in prehospital recognition and management of EHS, based on domestic and international research findings and combined with practical scenarios. It also provides an accurate prehospital management plan according to the China Expert Consensus on Diagnosis and Treatment of Heatstroke, aiming to reduce or avoid irreversible damage to EHS patients caused by these misunderstandings and to decrease the incidence, disability rate, and mortality rate of EHS.关键词：exertional heat stroke;prehospital recognition;prehospital management;misunderstandings122|368|0更新时间：2024-08-14
Expert Review
- “在急性轻型缺血性卒中治疗领域，民航总医院神经内科专家通过回顾性分析86例患者数据，发现高同型半胱氨酸血症是静脉溶栓后早期神经功能恶化的独立危险因素，为临床治疗提供了重要参考。”
摘要：ObjectiveTo investigate the risk factors for early neurological deterioration (END) following intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) acute mild ischemic stroke (AMIS) patients.MethodsEighty-six patients with AMIS who underwent intravenous thrombolysis with rt-PA in the Department of Neurology, Civil Aviation General Hospital between January 2019 and October 2022 were retrospectively analyzed. Patients were categorized into END group (n=8) and non-END group (n=78) based on the presence of END within 24 hours after thrombolysis (NIHSS score increased by ≥2 points within 24 hours after intravenous thrombolysis). Baseline characteristics, including age, gender, past medical history (hypertension, diabetes, hyperlipidemia, etc.), smoking history, pre-thrombolysis NIHSS score, homocysteine level, fibrinogen level, and post-thrombolysis bleeding transformation were documented for each patient. A multivariate logistic regression analysis was conducted to access the risk factors associated with END following intravenous thrombolysis in AMIS.ResultsThere were significant differences in homocysteine and fibrinogen levels, as well as bleeding transformation after thrombolysis between the two groups (P<0.05). In contrast, other factors such as age, gender, past medical history, pre-thrombolysis NIHSS score, and other imaging features were not statistically significant (P>0.05). Multivariate logistic regression analysis revealed that elevated homocysteine level was independently linked to risk of END after intravenous thrombolysis in AMIS, with an odds ratio of 1.074(95%CI 1.011-1.142, P=0.021).ConclusionsHyperhomocysteinemia emerges as an independent risk factor for END following intravenous thrombolysis in patients with AMIS.关键词：acute mild ischemic stroke;intravenous thrombolysis;homocysteine;early neurological deterioration131|428|0更新时间：2024-08-14 - “最新研究发现，尼妥珠单抗联合TP方案诱导化疗对局部晚期鼻咽癌具有显著疗效和安全性。研究显示，EGFR表达强度与治疗效果相关，联合方案能显著提高颈部淋巴结客观缓解率，同时降低白细胞减少和胃肠道反应发生率。”
摘要：ObjectiveTo investigate the short-term efficacy and safety of chemotherapy induced by nimotuzumab (NTZ) combined with TP regimen and sequential concurrent chemoradiotherapy in patients with epidermal growth factor receptor positive(EGFR-positive) locally advanced nasopharyngeal carcinoma.MethodsA total of 48 patients with stage Ⅲ to IV A nasopharyngeal carcinoma in Guizhou Provincial People's Hospital from January 2020 to December 2022 were prospectively enrolled, and were randomized into two groups: NTP (NTZ+docetaxel/albumin-paclitaxel+cisplatin) group and TP (Docetaxel/albumin-paclitaxel+cisplatin) group(24 cases per group) by random number table method. After 2 or 3 cycles of induction chemotherapy in NTP group, NTZ was sequentially used in combination with cisplatin for concurrent chemoradiotherapy. Immunohistochemistry was used to detect the EGFR expression level, exploring EGFR expression intensity and the therapeutic effect of NTZ in NTP group patients. Meanwhile, short-term efficacy, withdrawal rate and toxic side effects were compared between the two groups after induction chemotherapy.ResultsIn NTP group, the positive expression rate of EGFR was 100%, and EGFR expression intensity significantly correlated with the efficacy of NTZ-combined induction therapy (P<0.05). After induction chemotherapy, the objective response rate (ORR) of cervical lymph nodes in NTP group was significantly higher than that in TP group (75% vs. 45.8%, P=0.039). The primary lesion ORR and overall (primary lesion and cervical lymph node) ORR showed no significant difference between the two groups(P>0.05). Comparison of adverse reactions between the two groups during induction therapy: leukopenia and gastrointestinal reaction in NTP group were lower than those in TP group (P<0.05), but rash was higher than those in TP group (P<0.05). There was no significant difference in liver function, hemoglobin and thrombocytopenia between two groups (P>0.05).ConclusionsEGFR expression intensity varies in nasopharyngeal carcinoma tissues, with higher levels indicating greater clinical benefit of combined induction therapy with NTZ. NTZ combined with TP induction regimen demonstrates good short-term efficacy and safety for cervical lymph nodes in patients with locally advanced nasopharyngeal carcinoma.关键词：nasopharyngeal carcinoma;induction chemotherapy;EGFR;nimotuzumab;adverse reactions80|306|0更新时间：2024-08-14 - “最新研究进展：基于生命体征时序数据和机器学习算法，成功开发并验证了创伤致死性大出血伤情动态预测模型，为早期诊断和动态预测提供解决方案。”
摘要：ObjectiveTo establish a dynamic prediction model of fatal massive hemorrhage in trauma based on the vital signs time series data and machine learning algorithms.MethodsRetrospectively analyze the vital signs time series data of 7522 patients with trauma in the Medical Information Mart for Intensive Care-Ⅳ (MIMIC-Ⅳ) database from 2008 to 2019. According to the occurrence of posttraumatic fatal massive hemorrhage, the patients were divided into two groups: fatal massive hemorrhage group (n=283) and non-fatal massive hemorrhage group (n=7239). Six machine learning algorithms, including logistic regression (LR), support vector machine (SVM), random forests (RF), adaptive boosting (AdaBoost), gated recurrent unit (GRU), and GRU-D were used to develop a dynamic prediction models of fatal massive hemorrhage in trauma. The probability of fatal massive hemorrhage in the following 1, 2, and 3 h was dynamically predicted. The performance of the models was evaluated by accuracy, sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and area under receiver operating characteristic curve (AUC). The models were externally validated based on the trauma database of the Chinese PLA General Hospital.ResultsIn the MIMIC-Ⅳ database, the set of dynamic prediction models based on the GRU-D algorithm was the best. The AUC for predicting fatal major bleeding in the next 1, 2, and 3 h were 0.946±0.029, 0.940±0.032, and 0.943±0.034, respectively, and there was no significant difference (P=0.905). In the trauma dataset, GRU-D model achieved the best external validation effect. The AUC for predicting fatal major bleeding in the next 1, 2, and 3 h were 0.779±0.013, 0.780±0.008, and 0.778±0.009, respectively, and there was no significant difference (P=0.181). This set of models was deployed in a public web calculator and hospital emergency department information system, which is convenient for the public and medical staff to use and validate the model.ConclusionA set of dynamic prediction models has been successfully developed and validated, which is greatly significant for the early diagnosis and dynamic prediction of fatal massive hemorrhage in trauma.关键词：wounds and injuries;massive hemorrhage;machine learning;assistant diagnosis88|537|0更新时间：2024-08-14 - “最新研究揭示，阻塞性睡眠呼吸暂停与高血压存在双向因果关系，其中高血压对睡眠呼吸暂停的影响尤为显著。研究采用双向孟德尔随机化分析方法，为深入理解两者关联提供了科学依据。”
摘要：ObjectiveTo investigate the causal relationship between obstructive sleep apnea (OSA) and hypertension using bidirectional Mendelian randomization (MR).MethodsGenetic data for OSA were obtained from the Genome-wide association study (GWAS) of FinnGen Biobank, including 16 761 cases and 201 194 controls, from which 5 single-nucleotide polymorphisms (SNPs) were screened as instrumental variables (IVs) for OSA. Genetic data for hypertension were obtained from GWAS of UK Biobank, including 124 227 cases and 337 653 controls from which 214 SNPs were selected as IVs for hypertension. Multiple MR methods, mainly Inverse variance weighted (IVW), were used for analysis. Sensitivity analysis of MR results was performed using MR-Egger regression et al, and IVs were evaluated using F values.ResultsOSA was associated with an increased risk of hypertension(OR=1.053, 95%CI 1.019-1.089, P<0.01), and hypertension was significantly associated with the risk of developing OSA (OR=1.812, 95%CI 1.354-2.425, P<0.001). Heterogeneity was observed in both two-way outcomes (OSA→ hypertension, P<0.001; hypertension→ OSA, P<0.001), but no evidence of horizontal pleiotropy was detected (OSA→ hypertension, P=0.666; hypertension→ OSA,P=0.556). The IVs selected in this study were strong instrumental variables for both OSA and hypertension (OSA-IVs F=14.695; hypertension-IVs F=39.624).ConclusionsOur findings indicate a bidirectional causal relationship between OSA and hypertension, with a particularly significant effect of hypertension on the development of OSA.关键词：obstructive sleep apnea;hypertension;Mendelian randomization;bidirectional;causality142|1881|0更新时间：2024-08-14 -
Effect of high expression of endonuclease meiotic 1 on the prognosis of hepatocellular carcinoma AI导读
“最新研究发现，肝细胞癌中减数分裂内切酶1(EME1)的高表达与患者不良预后密切相关，可能成为治疗的新靶点。”
摘要：ObjectiveTo elucidate the clinical significance of high expression levels of endonuclease meiosis 1 (EME1) in the prognosis of hepatocellular carcinoma (HCC).MethodsThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to screen and analyze differential gene expression between HCC and non-tumor tissues. A retrospective collection of liver tissue samples from 80 HCC patients who underwent hepatectomy in the Fifth Medical Center of Chinese PLA General Hospital between January 2010 and December 2014 was performed. Immunohistochemistry analysis was employed to detect the EME1 expression levels. Survival analysis was then conducted to assess the impact of EME1 expression on 5-year postoperative survival rate of HCC patients. Additionally, gene enrichment analysis was applied to predict the function of EME1 in HCC.ResultsA total of 371 HCC tissue samples and 50 non-tumor liver tissue samples from TCGA database were analyzed, revealing significantly higher EME1 expression in HCC tissues. Microarray analysis of 107 samples within the GEO database (70 HCC tissues and 37 non-tumor tissues) confirmed that EME1 mRNA expression was markedly elevated in HCC tissues compared with non-tumor tissues (P<0.05). The 5-year overall survival (OS) rate was notably lower in high EME1 expression group than that in low expression group (44.1% vs. 53.0%, P<0.05). Semi-quantitative immunohistochemistry analysis demonstrated that patients with high EME1 expression had a significantly lower OS rate than those with low EME1 expression (32.8% vs. 45.0%, P<0.05). Multivariate COX regression analysis identified that high EME1 expression (HR=2.234, 95%CI 1.073-4.649, P=0.032) and advanced China liver caner (CNLC) staging (HR=4.317, 95%CI 1.799-10.359, P=0.001) were independent risk factors for the 5-year OS of post-operation patients with HCC.ConclusionElevated EME1 expression in HCC tissues correlates with an adverse prognosis of HCC and suggests that EME1 could serve as a potential therapeutic target for HCC.关键词：hepatocellular carcinoma;endonuclease meiotic 1;immunohistochemistry;survival analysis60|158|0更新时间：2024-08-14 - “最新研究揭示遗传性肌病伴早期呼吸衰竭(HMERF)的临床特征和基因突变，为诊断和治疗提供新见解。研究发现，HMERF患者多表现为四肢无力和呼吸困难，肌肉MRI显示特定脂肪浸润，且TTN基因突变是主要遗传标记。本病例中，患者携带TTN基因的两个新突变位点，为HMERF的遗传学研究增添新视角。”
摘要：ObjectiveTo report the clinicopathological features, gene mutation sites, diagnosis and treatment of a case of hereditary myopathy with early respiratory failure (HMERF), and review the literature to enhance the understanding of the disease.MethodsA retrospective analysis was conducted on the clinical data, imaging examinations, histopathological and genetic sequencing results, as well as the diagnosis and treatment of a case of HMERF as the initial presenting symptom, admitted to Sichuan Provincial People's Hospital in April 2021. The clinical characteristics of Chinese patients with HMERF were summarized in conjunction with literature reports.ResultsThis patient presented with limb weakness and progressive dyspnea. Magnetic resonance imaging (MRI) showed selective fat infiltration of the medial head of calf gastrocnemius muscle. Two mutation sites in titin (TTN) gene inherited from both parents were identified, exon 341 c.94828G>A (P.a31610t) and exon 50 c.14915C>T (P.S.4972L), leading to the diagnosis of HMERF. The patient received supportive therapy. The PubMed database was searched and 15 cases of HMERF were diagnosed in Chinese patients over the past decade. The onset age of these patients was (26.1±17.0) years, predominantly affecting males. All patients exhibited mutations in TTN gene. The most prevalent mutation was identified as c.95195C>T (p.P31732L), followed by c.95134T>C (p.C31712R).ConclusionsHMERF is a rare genetic disease caused by genetic mutation, with skeletal muscle weakness and respiratory muscle weakness as the main clinical manifestations. Clinical symptoms can be atypical, and exon 344 of TTN gene is a common mutation site. The mutation sites in this case, located at exon 341 c.94828G>A (P.a31610t) and exon 50 c.14915C>T (P.S4972L) of the TTN gene, may represent novel genetic markers for HMERF.关键词：hereditary myopathy with early respiratory failure;titin;gene mutation54|76|0更新时间：2024-08-14 - “在胸科腔镜肺部病损切除术中，艾司氯胺酮联合右美托咪定的零阿片术后自控镇痛策略，有效降低术后恶心呕吐发生率，提高患者舒适度。”摘要：ObjectiveTo explore the application effect of opioid-free postoperative patient-controlled analgesia strategy in thoracic endoscopic resection of lung lesions.MethodsThis study is a single center, double-blind, prospective, open label, randomized controlled trial. Ninety patients with lung surgery under thoracic endoscope in the Second Affiliated Hospital of Chongqing Medical University were selected from November 2021 to April 2023, and divided into three groups, according to the random number table method including esketamine and dexmedetomidine (esKDex group, n=30), sufentanil and dexmedetomidine (sFDex group, n=30) and tramadol and dexmedetomidine (TraDex group, n=30). The incidence of postoperative nausea and vomiting (PONV), vital signs related indicators, visual analogue scale (VAS) score, Ramsay sedation (RSS) score, Bruggrmann comfort scale (BCS) score and mini-mental state examination (MMSE) score were compared among the 3 groups within 48 hours after surgery.ResultsWithin 48 h after surgery, the incidence of PONV in esKDex group was lower than that in sFDex group and TraDex group [10.0%(3/30) vs. 20.0%(6/30) vs. 20.0%(6/30), P<0.001]. The VAS scores in esKDex group and sFDex group at 2 h and 4 h after surgery were lower than those in TraDex group (2 h after surgery: P=0.001, 0.001; 4 h after surgery: P=0.027, 0.024). The VAS scores at 24 h and 48 h after surgery were higher than those in TraDex group (24 h after surgery: P=0.008, 0.029; 48 h after surgery: P=0.005, 0.005). The BCS scores of esKDex group and sFDex group at 24 h and 48 h after surgery were lower than those in TraDex group (24 h after surgery: P=0.017, 0.007; 48 h after surgery: P=0.005, 0.007). There was no significant difference between Ramsay scores and MMSE scores among the three groups within 48 h after surgery (P>0.05).ConclusionThe strategy of opioid-free postoperative patient-controlled analgesia (esketamine and dexmedetomidine) can reduce the incidence of PONV under the premise of satisfying the sedation and analgesia of patients after thoracic endoscopic surgery.关键词：thoracic surgery;postoperative analgesia;multimodal analgesia;opioid-free analgesia strategy52|310|0更新时间：2024-08-14
- “最新研究揭示，高血压1级（≥130/80 mmHg）显著增加糖尿病患者发生慢性肾脏病和估算肾小球滤过率下降的风险，为糖尿病肾病的早期干预提供了重要依据。”
摘要：ObjectiveTo investigate the effect of varying blood pressure stratification on renal function in the diabetic population.MethodsA prospective cohort study was conducted, enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007. The follow-up period was (8.6±4.0) years. Participants were categorized into four groups based on their baseline blood pressure levels: normal blood pressure (systolic blood pressure <120 mmHg and diastolic blood pressure <80 mmHg), elevated blood pressure (systolic blood pressure 120-130 mmHg and diastolic blood pressure <80 mmHg), stage 1 hypertension (systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg), and stage 2 hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure≥90 mmHg). The incidence density of chronic kidney disease (CKD) was compared among these groups. A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients, with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model. Sensitivity analysis was conducted after excluding cases of cardiovascular disease (CVD) during follow-up, and cases using antihypertensive and antidiabetic medications at baseline.Results(1) At baseline, stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index (BMI) compared to normal blood pressure group (P<0.05). (2) By the end of the follow-up, 2 294 cases of CKD were identified, including 1 117 cases of estimated glomerular filtration rate (eGFR) decline and 1 575 cases of urinary protein. The incidences density of CKD, eGFR decline and urinary protein for stage 1 hypertension group were 39.4, 16.3 and 25.5 per thousand person-years, respectively, all of which were statistically significant different from normal blood pressure group (log-rank test, P<0.01). (3) Multivariate Cox regression analysis revealed that, compared to the normal blood pressure group, stage 1 hypertension was associated with a 29% increased risk of CKD (HR=1.29, 95%CI 1.09-1.52) and a 40% increased risk of eGFR decline (HR=1.40, 95%CI 1.08-1.80) in diabetic individuals.ConclusionStage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals, with a particularly notable effect on the risk of eGFR decline.关键词：diabetes;stage 1 hypertension;renal impairment;estimated glomerular filtration rate;urine protein detection76|613|0更新时间：2024-08-14 - “在肾细胞癌治疗领域，解放军总医院第三医学中心泌尿外科的专家团队通过分析MDA、AOPP、Nrf2和GSH水平，揭示了老年患者腹腔镜肾部分切除术后急性肾损伤的潜在机制，为预防和治疗提供了新思路。”
摘要：ObjectiveTo analyze the correlation of malondialdehyde (MDA), advanced oxidation protein products (AOPP), nuclear factor erythroid-2 related factor 2 (Nrf2), glutathione (GSH) levels with postoperative acute kidney injury (AKI) among patients undergoing laparoscopic partial nephrectomy (LPN).MethodsA total of 110 patients with renal cell carcinoma who were admitted to the Department of Urology, the Third Medical Center of Chinese PLA General Hospital from February to August 2022 were included in the study. Patients were divided into AKI group (n=30) and non-AKI group (n=80) based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, and then divided into elderly AKI (>65 years old, n=14), middle-aged AKI (50-65 years old, n=16), elderly non-AKI (>65 years old, n=30), and middle-aged non-AKI (50-65 years old, n=50) four sub-groups based on age. Clinical characteristics and laboratory examination data were recorded. Venous blood was collected from the patients before the operation (T1), immediately after the surgery (T2), and 24 h after surgery (T3), and MDA, AOPP, Nrf2 and GSH levels were measured. MDA, AOPP, Nrf2 and GSH levels were compared between the four subgroups at different time points, and their correlation with the occurrence of AKI after LPN were explored. The risk factors for AKI after LPN were analyzed using the univariate and multivariate logistic regression.ResultsSpearman correlation analysis revealed that AKI was not associated with the MDA level at each time point (P>0.05), was positively associated with AOPP-T3 level (r=0.315, P=0.037), was negatively associated with the Nrf2-T3 level (r=-0.365, P=0.015) and GSH-T2 level (r=-0.338, P=0.025) in elderly patients after LPN. AKI was not associated with MDA, AOPP, Nrf2, and GSH levels (P>0.05) in middle-aged patients after LPN. Multivariate logistic regression analysis showed that BMI (OR=2.724, P=0.040) and surgically resected kidney volume (OR=1.309, P=0.049) were independent risk factors for AKI in elderly patients after LPN, GSH-T2 (OR=0.271, P=0.042) was an independent protective factor for AKI in elderly patients after LPN. Intraoperative colloid fluid intake (OR=1.006, P=0.007) was an independent risk factor for AKI in middle-aged patients after LPN, intraoperative urine output (OR=0.104, P=0.007) was an independent protective factor for AKI in middle-aged patients after LPN.ConclusionsThe AKI after LPN may be related to the increase of AOPP level and the decrease of Nrf2 and GSH levels in elderly patients, and the postoperative GSH is an independent protective factor for AKI in elderly patients after LPN. The correlation of AKI after LPN is not significant with the levels of MDA, AOPP, Nrf2 and GSH in the middle-aged patients.关键词：laparoscopic;partial nephrectomy;acute kidney injury;nuclear factor erythroid-2 related factor 2;glutathione52|382|0更新时间：2024-08-14
Clinical Research
- “最新研究发现，血管内皮生长因子(VEGF)抑制可导致小鼠卵泡发育障碍，其机制可能通过下调卵巢类固醇合成相关基因表达实现。该研究为卵巢功能研究提供了新视角。”
摘要：ObjectiveTo investigate the effect of vascular endothelial growth factor (VEGF) on the expression of genes related to ovarian steroid synthesis in mice and its underlying mechanism.MethodsA transgenic mouse model with tetracycline -reversible regulation of VEGF expression was used, and the genotype of mice was identified by polymerase chain reaction (PCR). Twenty mice were divided into normal VEGF expression group (Dox+, n=10) and VEGF expression inhibition group (Dox-, n=10) by feeding them doxycycline. Western blotting was used to detect the expression of VEGF protein in ovarian tissues. Fluorescence quantitative PCR was used to detect the mRNA expression of VEGF, KDR and genes known to play roles in follicle development, such as follicle-stimulating hormone (FSH) and inhibin B (INHBB). HE staining was used to observe changes in ovarian tissue. Total RNA was extracted from mouse ovarian tissues for transcriptome sequencing, and the relevant differential genes were analyzed by FPKM and log2FC values.ResultsCompared with the Dox+ group, the mRNA and protein levels of VEGF in the Dox- group significantly reduced, and the mRNA levels of KDR also significantly decreased (P<0.05). HE staining results showed that compared with the Dox+ group, follicular development was impaired and atresia follicles appeared in the Dox- group. Sequencing analysis identified that significant differences in follicular development-related genes and steroid synthesis-related genes between the two groups (P<0.05). Enrichment analysis showed that VEGF in mouse ovaries mainly regulates ovarian steroidogenesis and other pathways. Fluorescence quantitative PCR results demonstrated that compared with the Dox+ group, the follicular development-related genes (INHBB and FSHR) in the ovarian tissues of the Dox- group were significantly up-regulated (P<0.05), whereas the key genes of steroid synthesis (StAR, CYP11A1, 3β-HSD) were significantly down-regulated (P<0.05).The quantitative results were basically consistent with the sequencing results.ConclusionMice with inhibited VEGF exhibited ovarian follicular dysplasia, potentially due to the mechanism whereby VEGF inhibition downregulated the expression of genes associated with steroid synthesis, such as FSH and INHBB, thereby obstructing cholesterol metabolism.关键词：vascular endothelial growth factor;follicular development;sexual steroid hormones;transcriptome sequencing76|401|0更新时间：2024-08-14 - “最新研究发现，1α,25-二羟基维生素D3能有效缓解哮喘小鼠的气道炎症，其机制可能通过上调肺组织中SIRT1表达，抑制GATA-3表达，降低炎性因子IL-4、IL-5、IL-13水平。这一发现为哮喘治疗提供了新的解决方案。”
摘要：ObjectiveTo explore the effects of 1α,25-dihydroxyvitamin D3 on airway inflammation in asthmatic mice and the potential mechanisms.MethodsTwenty-four female BALB/c mice in SPF grade were randomly divided into three groups (n=8): control group, asthma group, and asthma+VD3 group. On the 1st, 8th, and 15th day, asthma group and asthma+VD3 group were given 0.2 ml ovalbumin (OVA) suspension for sensitization, while control group received 0.2 ml normal saline. On the 22-28th day, asthma group and asthma+VD3 group were challenged with 1% OVA atomization inhalation, while control group received an equal amount of normal saline atomization, for 30 minutes each time, once a day, for a continuous 7 days. Asthma+VD3 group was given intraperitoneal injection of 1α,25-dihydroxyvitamin D3 injection (4 μg/kg) 30 minutes before each atomization, while control group and asthma group were given an equal dose of normal saline. After the last challenge, all mice were anesthetized, and serum, bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected. HE staining and Periodic Acid Schiff (PAS) staining were used to observe the pathological changes in lung tissue and changes in airway mucus levels. ELISA was employed to detect serum IgE and inflammatory cytokines IL-4, IL-5 and IL-13 in BALF. Immunohistochemical technique and Western blotting were used to detect the expressions of SIRT1 and GATA-3 in mouse lung tissue.ResultsCompared with control group, asthma group had a significant increase in inflammatory cell infiltration around lung tissue, bronchia and accompanying perivascular, mainly characterized by eosinophils. Bronchial lumen stenosis, airway mucosal epithelial hyperplasia, and increased tracheal mucus secretion were also observed. The above changes in asthma+VD3 group were reduced compared with asthma group. Compared with control group, serum levels of IgE, and IL-4, IL-5, IL-13 inflammatory factors in BALF and GATA-3 in lung tissue were increased in asthma group (P<0.05), and SIRT1 level in lung tissue was significant decreased (P<0.05). Compared with asthma group, IgE level in serum, inflammatory factors of IL-4, IL-5 and IL-13 in BALF, and GATA-3 in lung tissue in asthma+VD3 group were decreased (P<0.05), and SIRT1 level in lung tissue was increased (P<0.05). Correlation analysis showed that the expression level of lung tissue SIRT1 was negatively correlated with the expression of GATA-3, serum IgG, and the levels of IL-4, IL-5, and IL-13 in BALF (P<0.05); the expression level of lung tissue GATA-3 was positively correlated with serum IgG and the levels of IL-4, IL-5, and IL-13 in BALF (P<0.05).Conclusion1α,25-dihydroxyvitamin D3 can alleviate airway inflammation in asthmatic mice, possibly by upregulating the expression of SIRT1 in lung tissue and inhibiting the expression of GATA-3, thereby inhibiting inflammatory factors (IL-4, IL-5, IL-13).关键词：bronchial asthma;1α,25-dihydroxyvitamin D3;SIRT1;GATA-3;airway inflammation68|285|0更新时间：2024-08-14 - “最新研究发现，诺卡酮能有效缓解轻度脑爆震伤大鼠的抑郁样行为，其机制可能与激活海马PKA/CREB/BDNF信号通路，促进神经发生有关。”
摘要：ObjectiveTo investigate the mechanism of nootkatone (NKT) in mitigating depression-like behavior caused by blast traumatic brain injury (TBI).MethodsThe rat bTBI depression-like model was established by simulating the shock wave parameters of blast overpressure (BOP of 60 kPa, 90 kPa, and 120 kPa) with a biological shock wave tube. After 14 days of exposure, we evaluated the depression-like behavior of rats using the tail suspension test and forced swimming test. We identified that the BOP (120 kPa) condition caused the most noticeable depressive behavior and used this condition for subsequent experiments. Thirty male SD rats were randomly divided into sham operation group, bTBI group (BOP of 120 kPa), and bTBI+NKT group [at 1 d after exposure to BOP of 120 kPa, giving NKT 10 mg/(kg·d) orally for 14 days], 10 in each group. After 14 days of exposure, the depression-like behavior of rats was evaluated by tail suspension test and forced swimming test. The expression levels of protein kinase A (PKA), phosphorylated cyclic adenosine monophosphate effector binding protein (pCREB), and brain-derived neurotrophic factor (BDNF) in the hippocampus of rat were determined by Western blotting. Immunohistochemistry was used to detect the generation of proliferating cell nuclear antigen (PCNA)-labeled neurons in the hippocampal dentate gyrus (DG).ResultsBOP of 90 kPa can cause depression-like in rats and BOP of 120 kPa can cause the most noticeable depressive behavior (P<0.05). Therefore, we selected the BOP exposure of 120 kPa for subsequent experiments. After 14 days of BOP exposure, compared with sham operation group, the immobility time of tad suspension test in bTBI group was prolonged (P<0.05), the latency of for ced swimming test was shortened, the immobility time was prolonged (P<0.05), the expression levels of PKA, pCREB and BDNF protein in hippocampus were lowered (P<0.05), and the number of PCNA-labeled neurons in hippocampal DG area was reduced (P<0.05); compared with the bTBI group, the immobility time of tail suspension test in bTBI+NKT group was shortened (P<0.05), the latency of forced swimming test was prolonged, the immobility time was shortened (P<0.05), the expression levels of PKA, pCREB and BDNF protein in hippocampus were increased (P<0.05), and the number of PCNA-labeled neurons in hippocampal DG area was increased (P<0.05).ConclusionsEarly treatment with NKT can improve depression-like behavior in mild bTBI rats. The mechanism may be related to the up-regulation of the PKA-CREB-BDNF signaling pathway and increased expression levels of pCREB and BDNF in the hippocampus, which results in increased neuron numbers in the DG region of the hippocampus.关键词：blast traumatic brain injury;depression;PKA/CREB/BDNF signaling pathway;hippocampal;blast shock wave53|255|0更新时间：2024-08-14 - “在颈动脉粥样硬化斑块研究领域，专家通过分析基因表达数据集，揭示了不稳定斑块的共调控差异表达基因及其分子相互作用。研究发现，IGFBP6可能成为预测不稳定颈动脉斑块的重要生物标志物，为该领域研究提供了新的解决方案。”
摘要：ObjectiveTo investigate the differentially expressed genes (DEGs) and their molecular interactions in unstable carotid atherosclerotic plaques.MethodsGene expression datasets related to carotid atherosclerotic plaques (GSE41571, GSE118481, and E-MTAB-2055) were downloaded from Gene Expression Omnibus (GEO) and European Bioinformatics Institute (EBI) ArrayExpress databases. The co-regulated DEGs in at least two datasets of unstable carotid plaques were merged and analyzed using Gene Ontology Biological Process (GO-BP), Kyoto Encyclopedia of Genes and Genomes (KEGG), Protein-Protein Interaction (PPI) Networks and subnetwork analysis, relationships between miRNAs/transcription factors and target genes, and drug-gene interaction database. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression levels of some DEGs in carotid plaques and plasma from 58 patients with carotid atherosclerosis.ResultsGO enrichment analysis showed that DEGs in unstable carotid atherosclerotic plaques were mainly enriched in genes related to inflammatory response and extracellular matrix structure genes. KEGG enrichment analysis indicated that upregulated DEGs in unstable carotid plaques were enriched in extracellular matrix receptor (ECM-receptor) interaction, PI3K-Akt, Hippo and transforming growth factor-β (TGF-β) signaling pathways, while downregulated DEGs were primarily enriched in lysosomes, phagosomes, and chemokines processes. PPI network analysis suggested that COL1A2, COL4A2, insulin-like growth factor binding protein 6 (IGFBP6), COL4A5, C1QA, CXCL10, CXCL2, CXCR4, and CSF1R may play important roles in PPI networks. Prediction of drug-gene interactions revealed that CSF1R had the most drug interaction, CXCL2 was most antagonized by drugs, and IGFBP6 was most activated by drugs. qRT-PCR showed that the expression level of IGFBP6 in unstable carotid plaques group was significantly lower than that in stable carotid plaques group (P<0.001). ELISA results showed that plasma concentration of IGFBP6 in unstable carotid plaques group was significantly lower than that in stable carotid plaques group (P<0.0001). Receiver operating characteristic (ROC) suggested that the area under the curve (AUC) for plasma IGFBP6 levels to identify unstable plaques was 0.894 (95%CI 0.810-0.977), with a cutoff value of 142.08 ng/ml.ConclusionIGFBP6 may become an important biomarker for predicting unstable carotid atherosclerotic plaques.关键词：atherosclerosis;apoplexy;bioinformatics;insulin-like growth factor binding protein 660|139|0更新时间：2024-08-14
Basic Research
- “最新研究揭示了TGR5在心血管系统中的重要作用，包括调节巨噬细胞、血管内膜功能、血管平滑肌、心肌细胞和线粒体代谢等，为心血管疾病治疗提供了新的理论依据。”摘要：Takeda G protein-coupled receptor 5 (TGR5) is a bile acid receptor located on the surface of cell membrane, widely distributed in many tissues and cells in the body, and can be directly activated by most bile acids in vivo. TGR5 plays an important role in various physiological and pathophysiological processes, including cellular Ca2+ transport, oxidative stress, cell proliferation, inflammatory responses, and mitochondrial metabolism, thereby maintaining mitochondrial homeostasis and vascular endothelial function, and inhibiting the progression of cardiovascular diseases such as atherosclerosis, myocardial hypertrophy, and cardiac remodeling after myocardial infarction. Currently, with the gradual clinical application of numerous bile acid and bile acid derivatives drugs, it is necessary to further investigate the role of TGR5 in the cardiovascular system, which is an important basis for clinical application of these new drugs. This review discusses the relationship between TGR5 and cardiovascular system from five perspectives: TGR5's involvement in regulating macrophages, endothelial function, vascular smooth muscle cells, cardiomyocytes, and mitochondrial metabolism. It summarizes the recent research progress, aiming to provide the theoretical basis for TGR5 as a novel therapeutic target for cardiovascular diseases.关键词：Takeda G protein coupled receptor 5;cardiovascular diseases;atherosclerosis;bile acid94|643|0更新时间：2024-08-14
- “最新研究揭示光动力疗法(PDT)在肿瘤治疗中的免疫效应机制，为未来临床应用提供新方向。”
摘要：As a novel tumor treatment, photodynamic therapy (PDT) has been widely used in clinical treatment of a variety of tumors due to its advantages, such as fewer adverse reactions, precise targeting and repeatability of treatment. Unlike conventional treatments, such as surgery, chemotherapy and radiotherapy, PDT not only eliminates the primary tumor but also effectively inhibits metastatic tumors by activating the body's immune response. However, the PDT-activated immune response is influenced by multiple factors, including the localization and dose of photosensitizer in the cells, light parameters, oxygen concentration in the tumor, and the integrity of immune function. This review summarizes the mechanisms behind the PDT-activated anti-tumor immune response, systematically examines the key influencing factors on the immune effect of PDT, and discusses the future development direction of PDT in cancer treatment.关键词：photodynamic therapy;innate immunity;specific immunity;influence factors77|768|0更新时间：2024-08-14 - “最新研究发现，肝内M1/M2型巨噬细胞在肝纤维化中发挥关键作用，其回输可延缓肝纤维化进程，为慢性肝病治疗提供新思路。”
摘要：Hepatic fibrosis refers to repeated or persistent inflammation and necrosis of liver parenchymal cells and excessive deposition of liver fibrous connective tissue caused by various etiologies, which is a necessary stage for chronic liver disease to develop into cirrhosis. Etiological treatment as antiviral therapy can reduce the inflammation of the liver tissues to a certain degree, but cannot completely stop the process of liver fibrosis. In recent years, researchers have found that intrahepatic macrophages play an important role in the occurrence and progression of hepatic fibrosis, among which M1/M2 macrophages have become the key to exploring macrophages to regulate hepatic fibrosis. This article will focus on the role and mechanism of intrahepatic M1/M2 macrophages in hepatic fibrosis.关键词：hepatic/liver fibrosis;macrophages;extracellular matrix72|1268|0更新时间：2024-08-14
Review
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